Localized delivery and retention of hydrogen sulfide causing regional lipid accumulation in mouse adipose tissues in vivo.

Therapeutical application of hydrogen sulfide (H(2)S) is limited due to the lack of delivery routes for specific organs and the rapid and wide dispersal of H(2)S in vivo. While H(2)S shows adipogenic effects in vitro, its in vivo impacts on obesity remain unclear. This study applies a H(2)S-slow-releasing hydrogel (H(2)S gel) to deliver H(2)S locally in subcutaneous adipose tissue and examines local lipid accumulation in mice. H(2)S is released from H(2)S gels within 6 h and lasts for 72 h, elevating H(2)S levels in local adipose tissue but not in the plasma. Localized H(2)S gel delivery causes significant lipid accumulation and larger lipid droplet diameter in mouse adipose tissues. The expressions of sterol regulatory element-binding protein, peroxisome proliferator-activated receptor-γ, adiponectin, and perilipin are all upregulated by H(2)S gel injections. Local delivery and retention of H(2)S in adipose tissues increase lipid accumulation more in wild-type than in cystathionine-γ-lyase knockout mice. This study confirms the feasibility of selectively delivering H(2)S via injectable hydrogels and their effectiveness in regulating targeted tissue functions. Furthermore, this work deepens our understanding of the role of H(2)S in obesity development under physiological conditions and offers a practical implementation strategy for H(2)S-based therapeutic interventions.